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Stimulation of reactive oxygen species and collagen synthesis by angiotensin II in cardiac fibroblasts

机译:血管紧张素Ⅱ刺激心脏成纤维细胞中的活性氧和胶原合成

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摘要

Superoxide anion generated by NAD(P)H-oxidase has an important role in the pathogenesis of cardiovascular diseases and scavenging superoxide anion can be considered as a reasonable therapeutic strategy. In hypertensive heart diseases there is a mutual reinforcement of reactive oxygen species (ROS) and angiotensin II (ANG II). ANG II increases the NAD(P)H-dependent superoxide anion production and the intracellular generation of ROS in cardiac fibroblasts and apocynin, a membrane NAD(P)H oxidase inhibitor, abrogates this rise. ANG II also stimulates the collagen production, the collagen I and III content and mRNA expression in cardiac fibroblasts and apocynin abolishes this induction. In this review we demonstrate that scavenging superoxide anion by tempol or EUK-8 or administration of PEG-superoxide dismutase (SOD) inhibits collagen production in cardiac fibroblasts. On the contrary increasing superoxide anion formation by inhibition of SOD stimulates collagen production. A vital role of SOD and the generated ROS can be suggested in the regulation and organization of collagen in cardiac fibroblasts. Specific pharmacological intervention with SOD mimetics can probably be an alternative approach for reducing myocardial fibrosis.
机译:NAD(P)H-氧化酶产生的超氧阴离子在心血管疾病的发病机理中具有重要作用,清除超氧阴离子可被视为一种合理的治疗策略。在高血压心脏病中,活性氧(ROS)和血管紧张素II(ANG II)相互增强。 ANG II可增加NAD(P)H依赖的超氧阴离子的产生,并增加心肌成纤维细胞和细胞膜AADcynin(一种膜NAD(P)H氧化酶抑制剂)中ROS的细胞内生成,从而消除了这种上升。 ANG II还刺激心肌成纤维细胞中胶原蛋白的产生,胶原蛋白I和III的含量以及mRNA表达,而载脂蛋白A消除了这种诱导作用。在这篇综述中,我们证明了通过tempol或EUK-8清除超氧化物阴离子或使用PEG-超氧化物歧化酶(SOD)抑制了心脏成纤维细胞中胶原蛋白的产生。相反,通过抑制SOD来增加超氧阴离子的形成会刺激胶原蛋白的产生。在心脏成纤维细胞的胶原蛋白的调节和组织中,SOD和产生的ROS可能起着至关重要的作用。用SOD模拟物进行特殊的药理干预可能是减少心肌纤维化的另一种方法。

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